BeOne, a Swiss drug company that started in China as BeiGene, is making waves in the blood cancer treatment market. Their popular drug, Brukinsa, is outperforming strong competitors like Imbruvica from Johnson & Johnson and AbbVie, as well as AstraZeneca’s Calquence. BeOne is not stopping there; they have more promising treatments in the works, aiming to make a significant impact on leukemia and lymphoma treatments. One of these is sonrotoclax, which is expected to receive accelerated approval by mid-next year. Unlike Brukinsa, which stops a protein called BTK to prevent cancer from spreading, sonrotoclax works differently and is more powerful and selective. BeOne is focusing on B-cell cancers like chronic lymphocytic leukemia and small lymphocytic lymphoma, putting them in direct competition with big pharmaceutical companies. They are also gathering long-term results for Brukinsa and preparing for sonrotoclax’s accelerated approval. Additionally, they have other potential first-in-class treatments in development. To learn more about the challenges and opportunities in blood cancer treatment, the company’s unique position, and the ongoing trials, we spoke with Dr. Amit Agarwal, BeOne’s chief medical officer of hematology. The interview has been edited for brevity and style. PHARMAVOICE: How do you see the current state of the blood cancer treatment industry? What’s driving progress in the field now that wasn’t true a few years ago? DR. AMIT AGARWAL: The progress in blood cancer treatment has been remarkable. Compared to 10 or 15 years ago, we’ve made significant strides. Blood cancers are easier to study because we can access tissue samples anytime. Technological advancements have brought impressive treatments, from small molecule inhibitors like Gleevec to cell therapies and biologics. Regulatory bodies have also been more open to surrogate endpoints, allowing for faster approvals. However, there’s still work to be done. What are the biggest challenges in the next few years? The next big challenge is achieving functional cures, where patients can either stay on treatment or live a normal lifespan. We’re making progress, but there’s still a huge unmet need, especially in acute myeloid leukemia. Some diseases have seen benefits, and we’re moving towards giving patients a near-normal lifespan and quality of life. BeOne focuses on B-cell malignancies. What are the particular challenges there? With Brukinsa, we’ve made a significant impact on B-cell malignancies in five different indications. It’s become a cornerstone treatment for multiple diseases, thanks to our deep understanding of the biology. However, we need to see the long-term effects, over six, seven, or eight years, to truly understand the impact. Brukinsa has allowed us to do that, especially in chronic lymphocytic leukemia. We’re uniquely positioned as a company with all the necessary assets to make progress in blood cancer treatment. From Brukinsa as a foundational treatment to sonrotoclax with a broader indication base, and even degraders, we can build on our knowledge and expertise. You’ve mentioned the goal of long-term survival. Can you tell me about the Sequoia trial for Brukinsa in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma? The Sequoia study has a median follow-up of six years, and we’re looking at what happens to patients over a prolonged period. We’re monitoring progression events and subsequent treatments. If an older patient can see through the rest of their natural lifespan on Brukinsa, that’s a powerful outcome. The most important thing is how consistent the results are, and we’re starting to see the advantages become more apparent. Brukinsa is one of a few BTK inhibitors on the market. You’ve competed against the original, Imbruvica, in the Alpine study. What opportunities are you trying to capture? The key point from the study design is that Imbruvica was considered the standard of care, and we wanted to show that Brukinsa is superior head-to-head. We’ve demonstrated that, highlighting the importance of choosing the right BTK inhibitor for these patients. What makes one BTK inhibitor better or more effective than another? It goes back to the pharmacology. For B-cell malignancies, sustaining inhibition is critically important. Imbruvica’s biggest challenge was off-target effects, as it inhibited many different proteins in addition to BTK. Brukinsa is much cleaner, making it the leading BTK inhibitor. Sonrotoclax is a major pipeline candidate for BeOne. Can you tell me what you’re seeing as a monotherapy in mantle cell lymphoma, particularly with the current treatment landscape? This is our first data disclosure of the mantle cell results. We’re encouraged by the high response rate and several patients achieving a complete response with promising durability. For patients with limited treatment options, this could be an important choice. The FDA has given it a breakthrough therapy designation and priority review, validating our belief in its importance for mantle cell lymphoma patients. With that potency comes some toxicity challenges. How are you addressing those as you speak to regulators ahead of a decision next year? Sonrotoclax is more potent but also more selective and has a shorter half-life than other BCL-2 inhibitors like Venclexta. This makes it safer, and with over 2,000 patients treated, we’ve seen that to be the case. In studies like this, if a patient dies, even if it’s related to disease progression, it’s not uncommon and is captured as part of the treatment – an emergent death. Regulators understand the difference between disease-related and treatment-related deaths. This reflects how difficult this therapeutic area is. Now, you’re also combining Brukinsa and sonrotoclax in CLL and SLL. What makes them a good match? There’s interesting science behind it. Brukinsa effectively pushes cancer cells out of their hiding places, like lymph nodes or bone marrow, into the peripheral blood. Sonrotoclax then has the killing mechanism. We see in the data that patients are achieving minimal residual disease much faster than with any combination of a BTK and BCL, so this could be foundational for CLL in the future.